RESUMEN
BACKGROUND: Postmortem human brain studies provide the molecular, cellular, and circuitry levels of resolution essential for the development of mechanistically-novel interventions for cognitive deficits in schizophrenia. However, the absence of measures of premortem cognitive aptitude in postmortem subjects has presented a major challenge to interpreting the relationship between the severity of neural alterations and cognitive deficits within the same subjects. METHODS: To begin addressing this challenge, proxy measures of cognitive aptitude were evaluated in postmortem subjects (N = 507) meeting criteria for schizophrenia, major depressive or bipolar disorder, and unaffected comparison subjects. Specifically, highest levels of educational and occupational attainment of the decedent and their parents were obtained during postmortem psychological autopsies. RESULTS: Consistent with prior findings in living subjects, subjects with schizophrenia had the lowest educational and occupational attainment relative to all other subject groups, and they also failed to show the generational improvement in attainment observed in all other subject groups. CONCLUSIONS: Educational and occupational attainment data obtained during postmortem psychological autopsies can be used as proxy measures of premortem cognitive function to interrogate the neural substrate of cognitive dysfunction in schizophrenia.
Asunto(s)
Trastornos del Conocimiento/psicología , Cognición , Escolaridad , Ocupaciones , Esquizofrenia/patología , Psicología del Esquizofrénico , Adulto , Anciano , Autopsia , Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PadresRESUMEN
Pregnant women living with HIV are at risk for loss to follow-up and viral rebound after delivery. We conducted a retrospective cohort study of women with HIV who delivered at Parkland Hospital, Dallas, to identify factors associated with postpartum loss to HIV care 1 year after delivery. Logistic regression was used to identify factors predicting loss to follow-up. For a subset of women, we compared odds of viremia detectable at delivery and postpartum among women with higher versus lower pill burden regimens. We included 604 women with HIV who delivered between 2005 and 2015. Three hundred ninety-one (65%) women completed at least one visit with an HIV provider within 1 year of delivery. The follow-up rate among black, non-Hispanic women was 65%; 57% for white, non-Hispanic women; and 78% for Hispanic women. Women without follow-up presented for prenatal care later (17 vs. 11 weeks, p < 0.001), and were less likely to be on antiretroviral therapy at initial prenatal visit (29% vs. 49%, p < 0.001). Factors predicting loss to follow-up in multivariate analysis included low-level viremia at delivery [adjusted odds ratio (aOR) = 2.85, 95% confidence interval (CI) = 1.73-4.71] and failure to return for a postpartum visit (aOR = 3.19, 95% CI = 2.07-4.94). High antiretroviral pill burden (≥6 pills daily) was associated with viremia (>1000 copies/mL) at the first prenatal visit (OR = 8.7, 95% CI = 4.6-16.6) through 1 year postpartum (OR = 2.3, 95% CI = 1.2-4.4). Viremia at delivery, failure to return for a postpartum visit, and high pill burden during pregnancy are predictors of postpartum loss to HIV care.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Continuidad de la Atención al Paciente/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Perdida de Seguimiento , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Mujeres Embarazadas/psicología , Adulto , Femenino , Estudios de Seguimiento , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Periodo Posparto , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , Atención Prenatal , Estudios Retrospectivos , Carga Viral/estadística & datos numéricosRESUMEN
OBJECTIVE: Deficits in working memory and cognitive control in schizophrenia are associated with impairments in prefrontal cortical function, including altered gamma band oscillations. These abnormalities are thought to reflect a deficiency in the synchronization of pyramidal cell activity that is dependent, in part, on gamma-aminobutyric acid (GABA) neurotransmission through GABA type A (GABA(A)) receptors containing alpha(2) subunits. The authors conducted a proof-of-concept clinical trial designed to test the hypothesis that a novel compound with relatively selective agonist activity at GABA(A) receptors containing alpha(2) subunits would improve cognitive function and gamma band oscillations in individuals with schizophrenia. METHOD: Participants were male subjects (N=15) with chronic schizophrenia who were randomly assigned to receive 4 weeks of treatment with the study drug MK-0777, a benzodiazepine-like agent with selective activity at GABA(A) receptors containing alpha(2) or alpha(3) subunits, or a matched placebo in a double-blind fashion. Outcome measures were the Brief Psychiatric Rating Scale (BPRS), Repeatable Battery for the Assessment of Neuropsychological Status, three tests of working memory and/or cognitive control (N-back, AX Continuous Performance Test, and Preparing to Overcome Prepotency), and EEG measures of gamma band oscillations induced during the Preparing to Overcome Prepotency task. RESULTS: Compared with placebo, the MK-0777 compound was associated with improved performance on the N-back, AX Continuous Performance Test, and Preparing to Overcome Prepotency tasks. The compound was also associated with increased frontal gamma band power during the Preparing to Overcome Prepotency task. No effects of the MK-0777 compound were detected in BPRS or Repeatable Battery for the Assessment of Neuropsychological Status scores, with the exception of improvement on the Repeatable Battery for the Assessment of Neuropsychological Status delayed memory index. The MK-0777 agent was well-tolerated. CONCLUSIONS: These findings provide preliminary support for the hypothesis that enhanced GABA activity at alpha(2) subunit containing GABA(A) receptors improves behavioral and electrophysiological measures of prefrontal function in individuals with schizophrenia.